Metered continuous spray therapy and dispensing systems for same

ABSTRACT

A spray delivery system in combination with a scalp medication is provided which includes a portable container having a gas imperious container wall, a pressure source disposed within the container, and a selectively operable valve assembly affixed to the container. The scalp medication is in liquid form and is disposed within the container. The scalp medication comprises a hair growth stimulation or hair growth maintenance active ingredient in an amount sufficient to stimulate or maintain hair growth disposed within a pharmacologically acceptable carrier solution. The valve assembly of the system produces a 1 mL spray of said scalp medication within about 5 seconds following a single operation of said valve assembly. A method of treating alopecia using a continuous spray employing such a system is also provided. Both bag-on-valve (bag-in-can) and metered dose packages are disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present invention is a continuation of U.S. application Ser. No.13/213,619, filed Aug. 19, 2011 (F5890-00084), which is a divisional ofU.S. application Ser. No. 12/193,153, filed Aug. 18, 2008 (F5890-00081),which is a continuation-in-part of U.S. application Ser. No. 11/677,777,filed Feb. 22, 2007 (F5890-00075), the entirety of which is incorporatedherein by reference.

FIELD OF THE INVENTION

The present invention relates to scalp medications generally, andparticularly those for treating alopecia.

BACKGROUND OF THE INVENTION

Alopecia, the loss of hair in men and women, involves a gradual decreaseof scalp hair density in adults, with a transformation of terminal tovellus hairs which become lost as a result of familial increasedsusceptibility of hair follicles to androgen secretion followingpuberty. Two areas of the scalp are commonly affected in men, asevidenced by a receding frontal and bilateral triangular temple hairlines, and a balding patch on the vertex, which may progress to completemale pattern baldness. In females, a diffuse partial hair loss in thecentral parietal area of the scalp with preservation of the frontal andtemporal hair lines is most common.

One of the more common therapies for alopecia is minoxidil, which hasbeen proven to be an effective hair growth stimulator that can bothmaintain and increase scalp hair counts. Minoxidil was first used as apatent antihypertensive drug. It was later discovered that Minoxidil hadpositive effects on hair growth when applied topically to the scalp.Minoxidil was first mass marketed as Rogaine® lotion by Upjohn, Inc. forthe treatment of hair loss in the late 1980s. Rogaine® lotion stillremains the only FDA approved topical medication for the treatment ofhair loss in the United States, as of this date. The directionsassociated with traditional minoxidil lotions, such as Rogaine® lotion,now manufactured by Johnson and Johnson, is that a total dose of 1 mLminoxidil topical solution should be applied twice per day to the scalp,beginning at the centre of the affected area. Each 1 mL of minoxidilsolution contains 20 mg of minoxidil for 2% solutions and 50 mg ofminoxidil for 5% solutions. This dose should be used regardless of thesize of the affected area. The total daily dose should not exceed 2 mL.The method of application varies according to the disposable applicatorused. Packages contain several applicator options, including a droppermarked with a 1-mL calibration, a spray applicator, and anextended-spray applicator, which is ideal for long hair. Six pumps ofthe applicators release 1 mL of minoxidil. Because systemic absorptioncould affect blood pressure, the patient should not inhale the aerosolgenerated by the spray applicators.

Although the following systemic effects have not been associated withthe topical use of minoxidil topical solution, there is some absorptionof minoxidil from the skin and the potential exists for systemic effectssuch as tachycardia, angina, edema or potentiation of the orthostatichypotension produced by guanethidine. Systemically absorbed minoxidil issecreted in human milk.

The application times for minoxidil should be at least four hours apart,suggesting that the best times to apply the product would be right afterthe morning shower, and before bed at night. The traditional 5%minoxidil Rogaine® lotion utilizes as much as 50% by volume propyleneglycol (20% v/v of propylene glycol for 2% minoxidil) as a vehicle forextending the delivery of the active medication to the scalp, and forensuring that the applied minoxidil is evenly spread across the affectedarea and easily absorbed into the skin. Propylene glycol and ethanolalcohol are also used to solubilize minoxidil. The problem associatedwith smearing copious amounts of propylene glycol on one's scalp is thatit leaves the hair and scalp with a greasy texture for an extendedperiod of time after the application. The resulting appearance is oftenunflattering. It also leaves the hair looking matted down and eventhinner than it really is, which may be considered an unfortunate stepin the wrong direction for a hair loss treatment.

Another issue associated with propylene glycol is that it can irritatethe user's scalp, resulting in itching, flaking, redness of the scalp,oiliness of the scalp, excessive dandruff, and even peeling in somecases. Because of these effects, the use of traditional minoxidilsolution was not an option for many hair loss sufferers, and glycerineversions of the popular medication have been developed, available byprescription from Minoxidil.com.

Johnson and Johnson is currently marketing Rogaine® Foam, which deliversminoxidil to the scalp in a manner that is just as effective as thetraditional propylene glycol based minoxidil lotions, but without someof the mess or unpleasantness. Rogaine® Foam is designed to retain its“foamy” texture at room temperature, but quickly liquefies, spurringquick skin absorption at body temperature.

Fast skin absorption by Rogaine® Foam means that the active ingredientof Rogaine® Foam, minoxidil, will be readily absorbed into the hand ofthe user, where it clearly is not intended to be absorbed.Over-absorption of minoxidil can result in vision changes, chest painand fast or irregular heart beat. Women exposed to over-absorption ofminoxidil may experience additional unwanted facial hair growth.Additionally, minoxidil may pass from mother to child through breastmilk. It is for these and other reasons that the Rogaine® Foam packageinsert suggests that the user rinse his or her hand under cold waterbefore applying the foam, to slow down absorption of the activeingredient into the hand. This, of course, requires another step (ortwo, if the user also dries his or her hand, as recommended by themanufacturer) in the application of the medication. It may also dilutethe concentration if one does not immediately dry one's hand afterwetting, and before applying the foam. In addition, hair does feel alittle stiffer after the application of the Rogaine® Foam and thesmearing of the foamy application, with or without a wet hand, can alsomat down hair styles, making them less natural looking.

Accordingly, there remains a need for further dispensing systems andmethods for scalp medications, including minoxidil and other products,such as DHT inhibitors, finesteride (Propecia®), copper peptides(Tricomin® and Folligen®), other DHT inhibitors (Dutasteride®),all-around treatments or combinations (Proxiphen®) androgen receptorblockers (Spirondactone®), corticosteroids, vitamin A derivatives(Retin-A®), tretinoin, azelaic acid, zinc, B6, grape seed extract,nicotinate and/or progesterone, which are easy to use and provide a morenatural appearance than conventionally applied propylene glycol-basedand foam-based products delivery systems.

SUMMARY OF THE INVENTION

In a first embodiment of the present invention, a spray delivery systemin combination with a scalp medication is provided. The system includesa portable container having a gas impervious container wall, a pressuresource disposed within the container and a selectively operable valveassembly affixed to the container. The scalp medication is in liquidform and is disposed within the container. It further comprises a hairgrowth stimulator or hair growth maintenance active ingredient in anamount sufficient to stimulate or maintain hair growth disposed within apharmacologically acceptable carrier solution. The valve assemblyproduces a 1 mL spray of said scalp medication within about 5 secondsfollowing a single operation of said valve assembly.

In a more preferred embodiment of the present invention, the scalpmedication comprises about 2-15% minoxidil or about 20 mg to about 150mg minoxidil per mL (2%-15% minoxidil). If a continuous spray package isemployed the spray is non-chilling (98.6° F.±5° F.), upon contact withskin, and is delivered quietly, under 60 decibels. The valve assemblycan be a 2-way valve, to enable both delivery of the scalp medicationand charging of the medication into the container, or product bag. Morepreferably the valve assembly produces a 1 mL spray of scalp medicationwithin about 1-5 seconds during a single operation of the valveassembly, for an effective delivery rate of about 0.2-1 mL/second. Thiswould be a significant improvement over currently available sprayapplicators used for generic minoxidil, which are known to require up tosix pumps of a pump dispenser to release 1 mL of minoxidil solution.

In a further embodiment of the present invention, a method of treatingalopecia is provided. The method includes providing a delivery systemcomprising a valve assembly affixed to a portable container containing apressure source surrounding a product bag containing minoxidil in anamount sufficient to stimulate or maintain hair growth, said minoxidildisposed within a pharmacologically acceptable carrier solution. Themethod further includes rotating the container and the valve assemblysuch that the valve assembly is at least partially below a portion ofthe container, actuating the valve assembly whereby the pressure sourcesurrounding the product bag is used to force minoxidil and the carriersolution out of the bag and continuously spraying a fine mist of saidminoxidil and said carrier solution onto an alopecia affected area ofthe scalp, whereby said fine mist contains about 1 mL of said minoxidiland said carrier solution and said continuous spraying step is less thanabout 5 seconds in duration for an effective delivery rate of greaterthan 0.2 mL/second. This method can be further employed in a continuousspraying step which is about 1-5 seconds, preferably about 1-3 seconds,and more preferably, about 2 seconds in duration during a singleoperation of the valve assembly. Preferably, the delivery systemdelivers a mist or spray which results in less than 5% of the dropletsin the mist or spray being respirable when the mist or spray is directedat a scalp.

In further improvements, the valve assembly can be selected to have anactuator valve diameter of less than 0.10 inches, preferably greaterthan about 0.001 inches, and more preferably, about 0.001 inches toabout 0.015 inches. This range enables the spray to be deliveredefficiently within the time constraints of typical use by consumers ofspray products of about 2 seconds. It is also desirable to maintain theactuator diameter within these preferred ranges so that the spraydroplets and volume are not so large as to cause dripping and runninessof the product, but just large enough to avoid the creation of too manyrespirable droplets.

In a further embodiment of the present invention, a continuous fine mistspray medication delivery system is provided. This system includes aselectively operable valve assembly affixed to a portable containercontaining a pressurized agent or pressure source and a product bagcontaining said spray medication. The product bag, also located in thecontainer, includes a sheet of gas impervious material having a barrierlayer therein. The gaseous propellant is substantially separated fromthe medication and its liquid carrier, at least prior to, and morepreferably, prior to and after selective operation of the valve assemblyto produce the fine mist. The continuous spray fine mist medicationpreferably comprises a hair growth stimulator or maintenance activeingredient, such as minoxidil, a DHT inhibitor, an androgen blocker, orother combinations thereof, in an amount sufficient to stimulate ormaintain hair growth, or both, disposed within a pharmacologicallyacceptable solution, for example, alcohol, with or without propyleneglycol, glycerin, dimethyl-isosorbide, or other “extenders” to permitbetter absorption.

It has been suggested that minoxidil is dose dependent, meaning thatpatients may have to increase the concentration of minoxidil over timein order to sustain the results. Consequently, it has been suggestedthat people should start using a lower strength formula, such as 2% v/v,and gradually move up the scale to 5% v/v, and then ultimately, to 12%v/v.

The present invention employs advanced spray technology to provide aquick, easy and effective application of scalp medications. In apreferred embodiment, a continuous spray of fine mist medication can beprovided at every angle, even upside down, enabling application to hardto reach places like the vertex of the scalp. The preferred spraytechnology uses environmentally safe, bag-in-can or metered dosetechnology to apply scalp medications, such as 2-15% v/v minoxidil(2,4-Diamino-6-piperidinopyrimidine 3-oxide) or DHT inhibitors, such as5-alpha-reductase inhibitors, such as finesteride (such as Propecia®brand, available from Merck, which is not recommended for women who areor may potentially become pregnant), or dutasteride (such as Avodart®,available from GlaxoSmithKline), copper peptides (Tricomin® andFolligen® brands), all-around treatments or combinations (Proxiphen®brand), androgen receptor blockers (Spirondactone® brand),corticosteroids, Retin-A® brand, tretinoin, azelaic acid, zinc, B6,grape seed extract, nicotinate and/or progesterone. The delivery systemsof this invention eliminate the uncomfortable twisting, reaching, andmost of the hand-drug contact associated with applying conventionalRogaine® liquid or Rogaine® Foam to the back of one's scalp.Accordingly, the active scalp medications are easier to apply thanRogaine® lotion, even when compared to Rogaine® lotion dispensed fromthe pump-spray bottle, since the delivery system of this invention canpreferably operate upside down without clogging or interruptions, anddispenses a preferred fine, even and continuous mist. Because thisdelivery system allows the scalp treatment to be applied evenly andcontinuously directly from the container onto the scalp, with little orno need for rubbing, absorption into the hand of the user, hand washingbefore and/or after use of the product, and unflattering matting of thehair due to rubbing can be eliminated.

The packaging of the bag-on-valve embodiments of this invention,preferably, also maintains total product integrity and freshness, andextends the useful life of the medication, even lengthening shelf-life.In addition, by using a preferred bag-in-can system, the scalpmedication can be separated from the pressurizing agent within apreferred hermetically sealed, multi-layered laminated pouch. The pouchcan maintain total formulation integrity, and pure product, preferably,can be dispensed without contamination by propellants. The spraymedication can have a quiet and non-chilling discharge, and allows allattitude)(360°) dispensing. By using existing through-the-valve aerosolfilling technology and equipment, the dispensing system of thisinvention can be designed to work with standard actuators and aluminumaerosol cans.

In a further embodiment of the present invention, a medication isprovided which includes a continuous even mist, including liquiddroplets, having an average diameter of about 1 nanometer to about 2000micrometers, said mist containing minoxidil in an amount sufficient tostimulate or maintain hair growth, in which said minoxidil is disposedwithin a pharmacologically acceptable carrier solution.

In a preferred embodiment of this invention, the spray medication can bedelivered quietly, under 50-60 decibels, and the continuous spray is,preferably, non-chilling upon contact with skin, or is approximately atambient temperature. The valve assembly can include a two-way valve andthe container may comprise an aluminum or steel can. The bag, desirably,includes at least one gusset so that it can expand when product isintroduced and lay on the bottom of the container to relieve stress onthe valve assembly.

The above and other features of the present invention will be betterunderstood from the following detailed description of the preferredembodiments of the invention that is provided in connection with theaccompanying drawing.

BRIEF DESCRIPTION OF THE DRAWING

The accompanying drawing illustrates a preferred embodiment of theinvention, as well as other information pertinent to the disclosure, inwhich:

FIG. 1 is a cross-sectional side elevational view showing a dispensingsystem (with a continuous spray in phantom) for housing the liquidmedication of this invention.

FIG. 2 is a partial cross-sectional side elevational view of a preferredmetered dose valve assembly; and

FIG. 3 is a partial cross-sectional side elevational view of a preferredcontinuous-flow valve assembly.

DETAILED DESCRIPTION

The present invention pertains to continuous spray medications, spraymedication dispensing systems, and methods for treating alopecia, inwhich a continuous mist of a scalp medication, such as minoxidil, DHTinhibitors and/or androgen blockers, for example, is provided in anamount sufficient to stimulate or maintain hair growth, or both, forexample. The minoxidil and/or other medication is disposed within apharmacologically acceptable carrier solution.

In the preferred embodiments of this invention, the continuous mists aredesigned to generate liquid droplets that are readily absorbed throughthe dermis, especially scalp tissue. Mist particle sizes range frommolecular clusters on the order of about 1 nanometer to about 2000micrometers, and more preferably, the spray should provide good coverageof the surface area without running onto unwanted areas of the face andneck

The preferred delivery system of the present invention includes the ABSbag-in-can system, such as the system available from CCL Container.These preferred systems are hand held, portable, and completelyself-contained. The ABS bag-in-can system separates the product from thepressurizing agent with a hermetically sealed, multi-layered laminatedpouch “bag”. The bag maintains total formulation integrity, and onlypure product, preferably, is dispensed, as opposed to other aerosolsystems that can mix the product with the gaseous propellant. Thismaintains the total product integrity, such as alcohol mixtures,solutions and suspensions of minoxidil and fenesteride formulations, andpotentially extends their shelf life. This system also has a quiet,non-chilling discharge, and allows for all-attitude)(360°) dispensing,permitting “upside-down” dispensing, which is highly desirable forspraying one's scalp. While Rogaine® lotion comes with its own pumpspray dispenser, the dispenser can not work upside down and,consequently, is very awkward to use on the vertex of one's scalp.Pump-spray containers such as this one are widely available and operateon the principle that when the nozzle pump is manually depressed,pressure is exerted on the liquid in the container, forcing it out ofthe spray nozzle. This pump dispenser is not continuous and produces avery uneven distribution of the product on one's scalp, generallydepositing a shot of 0.5 mL or more of the ingredients, in a heavysquirt to a small area of the scalp, which tends to cause the liquidmedication to run to where it is not needed, or worse, where it isdefinitely not recommended, such as on the face or the wearer's eyes.Moreover, conventional pump-spray dispensers such as these, attached toplastic bottles with plastic threads, are not hermetic, so the contentscan be affected by environmental conditions, which, in some cases,reduce the efficacy of the medication, and/or its solvent (also referredto as the “extender” or “carrier” solution).

Alternatively, this invention can employ a piston barrier package (alsoavailable from CCL Container since 1991), which also assures separationof the scalp medication from the propellant or pressurizing agent, formaintaining the purity and integrity of the formulation throughout itsconsumer life span. The system provides smooth controlled and uniformdischarge. In a piston barrier package, a piston is disposed in apreferred seamless tubular package between the propellant and theproduct. As the nozzle is activated, the piston is activated by thepropellant pressure in the lower part of the container, to push out theproduct through the nozzle. The preferred CCL version of this systemeliminates propellant bypass tendency common with other metal containersbecause of its seamless construction. It also comes with a speciallyengineered gassing hole at the bottom for improving sealing duringgassing and plugging operations.

Still in a further alternative example of this invention, a metered-dosevalve assembly can be used for dispensing the scalp medications of thisinvention. A metering valve typically regulates the volume of aformulation passing from a container to a metering chamber, whichdefines the maximum amount of the formulation that would be dispensed asthe next dose. The metering chamber typically fills with the formulationprior to the patient actuating the valve stem and thereby releasing thedose. The metering chamber is refilled with formulation after dispensingone dose so that the metering valve is ready to discharge the next dose.The metering chamber contains a formulation at all times except for thebrief time during which the valve stem is depressed by the user todischarge a dose. One example of a metered valve is disclosed in U.S.Pat. No. 6,783,027, which is hereby incorporated by reference.

In applying the proper amount of scalp medication to a consumer's scalp,the amount of hair growth stimulator or hair growth maintainer activethat will ultimately be deposited must be considered. It is commonlydesired to deliver from about 20 mg per mL (for 2% minoxidil solution)to about 50 mg per mL (for 5% minoxidil solution) to the scalp,regardless of the product form. In considering the use of spray packages(e.g., pressurized aerosol packages), it has been reported, see U.S.Pat. No. 6,783,027, that a typical consumer sprays consumer productssuch as antiperspirants (i.e., actuates the spray package) on averagefor 2 seconds, regardless of the amount of product being deliveredbecause the consumer usually doesn't see the amount of product that isultimately delivered. Therefore, when designing a package to spray ascalp medication, one must first adhere to this overriding consumerbehavior of continuously spraying for 2 seconds. It is understood thatspraying too much of a liquid or emission product may result in a wetrunny cosmetic feel, while spraying too little of a liquid or emulsionproduct may result in a unacceptable efficacy results.

In certain formulations of the present invention, a clear, preferablyno-rub, continuous spray of medication is provided. For example, analcohol base with little or no propylene glycol can be used. Higheramounts of propylene glycol, such as the 50% by volume used in Rogaine®lotion, can leave one's hair feeling flat and greasy. Glycerin anddimethyl-isosorbide, or combinations of glycerin, dimethyl-isosorbide,and/or propylene glycol (such as 50%/50% v/v or w/w glycerin-propyleneglycol, 80%/20% v/v or w/w glycerin-propylene glycol, 80%/10%/10% v/v/vor w/w/w dimethyl-isosorbide, glycerin and propylene glycol, or thelike) are more preferred for use as solvents and extenders for thisinvention. It has been reported that when dipropylene glycol additionsto minoxidil solutions are less than 5% by weight, the retention effectof minoxidil in the dermis is insufficient, and when the amount is morethan 40% by weight, the resulting preparation gives a bad feeling inuse. See U.S. Pat. No. 6,255,313.

In the preferred embodiments of this invention, the minoxidilformulations can include other ingredients, such as butane,butylated-hydroxytoluene, cetyl alcohol, citric acid, fragrance,glycerin, isobutane, lactic acid, polysorbate 60, propane, purifiedwater, SD alcohol 40B, and stearyl alcohol. In other formulations,sunscreen additives can be added, such as butyl methoxydibenzoylmethane,homosalate, ethylhexyl-salicylate, benzophenone-3, and diethylhexyl 2,6naphthalate. If water resistance is required, acrylates/octylacrylamidecopolymers (such as Dermacryl 79, available from National Starch) can beadded.

In a further compositional embodiment, a minoxidil spray lotionformulation includes at least about 2% v/v or 0.1% w/w, and preferably,about 2-15% v/v or 0.1-10% w/w minoxidil in a carrier solutioncomprising butane, butylated hydroxytoluene, cetylalcohol, citrix acid,fragrance, glycerin, isobutane, lactic acid, polysorbate 60, propane,purified water, SD alcohol 40B and stearyl alcohol.

In still a further embodiment, a minoxidil spray lotion formulationincludes about 2% v/v or 0.1% w/w, preferably about 2-15% v/v or 0.1-10%w/w minoxidil in a carrier solution comprising about 60% v/v or w/walcohol, about 20-50% v/v or w/w propylene glycol or glycerin andpurified water (balance). For greater sustained release, dipropyleneglycol can be used, as shown in U.S. Pat. No. 6,255,313, which is herebyincorporated by reference. Gel formulations containing minoxidil arealso contemplated by this invention and disclosed in U.S. Pat. No.5,225,189, which is also hereby incorporated by reference.

The preparations of the present invention are preferably adjusted to apH of 4-9, and more preferably about 5-8 when diluted with purifiedwater.

In more preferred embodiments of this invention, a continuous fine mistspray medication dispensing system 100 is provided, as shown in FIG. 1.The dispensing system includes a selectively operable valve assembly 10affixed to a container containing a pressure source or pressurizingagent. A product bag 12 containing said medication 25 in a liquid formis also provided. The bag 12 is disposed within the container andincludes a sheet of gas impervious material having a barrier layertherein. The gas impervious material helps to separate the medication 25in liquid form from the pressure source or pressurizing agent locatedelsewhere in the container, so as to keep the medication fresh andefficacious.

The fine spray mist medication is preferably, delivered quietly, under60 decibels (normal conversation, sewing machine, typewriter), and morepreferably, less than 40 decibels, or most preferably, about 30 decibelsor less (whisper, quiet library). It is a fine spray which is,preferably, non-chilling upon contact with skin, e.g., 98.6° F.±5° F.The valve assembly 10 is, preferably, a two-way valve. The container ispreferably made of a metal, such as aluminum or steel. The bag 12preferably includes at least one gusset 21 which expands from a positionof 23 a to a position 23 b when the liquid medication 25 reaches a fulllevel, at which time a fine mist 30 can be sprayed.

In a further embodiment of the present invention, a method of treatingalopecia is provided comprising a delivery system which includes a valveassembly 10 affixed to a container 13 containing a pressure source orpressurized agent, and a product bag containing minoxidil in an amountsufficient to stimulate or maintain hair growth disposed within apharmacologically acceptable carrier solution. The container 13 is thenrotated, and the valve assembly 10 is located such that the valveassembly 10 is at least partially below a portion of the container 13,or even upside down. The method further includes continuously spraying afine mist of said minoxidil and said carrier solution onto an alopeciaaffected area of the scalp. The applied solution is evenly distributedand no further action or rubbing is required, but some minor rubbing canbe employed, if necessary, to reach spots missed by the initialapplication.

In the preferred embodiments of the present invention, thepharmacologically acceptable carrier solution contains less than about50% v/v propylene glycol, and more preferably, less than about 20% v/v,and most preferably, less than about 5% v/v propylene glycol, or none atall. The carrier solution can also include, or alternatively comprise,glycerin, dimethyl-isosorbide, or a combination thereof, purified waterand an alcohol, such as SD alcohol, ethanol or isopropanol.

In still a further embodiment of the present invention, a spraymedication is provided which includes an even, continuous mistcontaining a scalp medication sufficient to stimulate or maintain hairgrowth. This embodiment of the scalp medication is disposed within apharmacologically carrier solution. This spray medication is transparenton the scalp and does not need to be rubbed into the skin of the scalpto be effective in stimulating or maintaining hair growth. Thismedication embodiment also, preferably, contains less than 20% v/vpropylene glycol for a 2% minoxidil solution.

With further reference to FIG. 1, the product dispensing system 100incorporates a product dispensing bag 12 in accordance with thepreferred embodiment of the present invention. The system includes acontainer 13 having external wall surface. A product dispensing bag 12has a gusseted bottom 23 and sealed side portion or portions. Theproduct dispensing bag 12 is also sealed around its top edge. A valveassembly 10 is attached to the product dispensing bag 12 via a valveconnector extending into the top surface of the container 13. FIG. 1illustrates a side elevational view of the product dispensing bag 12showing the bag being partially filled. The gusset 23 a can be opened,and then the expanded gusset 23 b can rest on the dome-shaped bottom 22.

After the container 13 is sealed, product is injected into the productdispensing bag via the preferred two-way valve and valve connector. Asthe bag 12 fills, it expands, and the gusseted bottom 23 spreads alongthe surface 22 of the bottom of the container 13. The gusseted bottom 23serves to prevent undue force on the seal between the valve 10 and thebag 12 when product is in the bag 12, because the mass of the productpreferably rests on the bottom of the container, rather than beingsupported by the bag/valve interface if the bag hangs in free space. Thegusseted bottom 23 controls the fill operation so that the bag fillsmore evenly and more fully. Furthermore, the gusset 23 improves bag fillcapacity for a given container size. Preferably, the height of thegusset 23 a (the distance between the bottom of the bag and the interiorseam of the gusset) extends for approximately eighty percent (80%) ofthe radius of the container 13.

It is further necessary to provide a source of dispensing pressure inthe container. In one method and system for providing a dispensingpressure that is regulated, a gas chamber consisting of the region inthe closed container surrounding the product bag 12, can be charged toan initial dispensing pressure. The pre-charge exerts pressure on theproduct dispensing bag 12 so that when the valve 10 is activated,product is forced from the bag 12 and out of the container 13. Withoutregulation, the pressure may steadily decline as product is dispensed.Such a pre-charge can be provided by using compressed gas in thecontainer surrounding the product bag, or by using a liquefied gaspropellant.

The preferred product dispensing bag and dispensing system of thepresent invention is further described in U.S. Pat. Nos. Re. 35,540;5,169,037 and 5,035,351, which are all hereby incorporated herein.

FIG. 1 further illustrates one type of a dispensing system configurationwherein the product dispensing bag 12 of the present invention is usedwith a pressure regulating mechanism. As described above, the productdispensing bag of the present invention can also be used in such systemsas compressed gas or liquefied hydrocarbon systems or any product-in-bagdispensing system where a pressure source surrounding the bag is used toforce product out of the bag, so that a continuous spray 30 can begenerated.

A product bag 12 having a gusseted bottom is disposed within containerwalls 13. A gas generating chamber 14 is preferably defined by the areabounded by the container walls 13 and the exterior of the product bag12. A first reactant 17, such as sodium bicarbonate, is disposed in abottom of the container in the gas generating chamber 14 and a pressureregulating mechanism 18 is also disposed in the gas generating chamber.The pressure regulating mechanism 18 includes a second reactant 19 whichcan be a liquid reactant, such as citric acid or vinegar. In oneembodiment, the pressure regulating mechanism is a hollow tube havingcheck valves 20 disposed at either end. When the second reactant 19combines with the first reactant, gas is generated within the gasgenerating chamber 14. The pressure regulating mechanism 18 is designedso that when a pressure outside of the tube exceeds a pressure inside ofthe tube, gas enters into the tube until pressure equilibrium isestablished. When the pressure inside of the tube exceeds the pressureoutside of the tube, the second liquid reactant 19 is forced from thetube into the gas generating chamber 14 so as to react with the firstreactant 17 to thereby generate gas within the gas generating chamberand reestablish pressure equilibrium between the pressure inside of thetube and the pressure surrounding the tube. The pressure generated inthe gas generating chamber 14 places the product bag 12 under pressureand, hence, also places the product 25 disposed within the bag 12 underpressure as well. Thus, when valve 10 is activated so as to dispenseproduct 25, product 25 is dispensed from the container under pressureproduced in the gas generating chamber.

While, preferably, sodium bicarbonate is used as the first reactant, andcitric acid as the second reactant, other reactants may be used. Also,solutions and slurries of the reactants may be used and the reactantsmay be interchanged, if desired.

The pressure regulating mechanism system 18 will be described in greaterdetail below. However, the tube is designed in such a manner so as toreact with the first reactant 17 to maintain a substantially constantdispensing pressure throughout the dispensing of the entire productdisposed in the product bag 12.

The initial pressure of the dispensing system is set when the productbag 12 is filled. As product 25 is introduced into the bag 12, thevolume of the bag 12 expands, thereby reducing the volume of the gasgenerating chamber to, in turn, increase the pressure within thatchamber. The increase in pressure of the chamber, in turn, results in anincrease in the gas pressure within the pressure regulating mechanism18. When the product bag 12 has been filled with product, a specificpressure is set in the gas generating chamber 14, and a gas pressure isalso set in the pressure regulating mechanism 18 as equilibrium isestablished between the pressure inside and the pressure outside of thatmechanism. The initial pressure is determined in accordance with theamount of product fill in conjunction with a given container size.Whenever the pressure in the gas generating chamber 14 drops due to theexpulsion of product and the concomitant expansion of the volume of thegas generating chamber, the pressure regulating mechanism expels apredetermined amount of second liquid reactant 19 which mixes with thefirst reactant 17 and regenerates pressure to reestablish the initiallycharged pressure within the gas generation chamber. The amount of citricacid or vinegar, for example, discharged is determined by the pressuredifferential between the container and tube head space and the volume ofgas in the tube. The act of filling the product bag 12 activates thepressure regulating system, charging it to a dispensing pressure. Thepressure regulating system further controls the dispensing pressure overthe course of dispensing the product from the container 13.

As further shown in FIG. 1, the product bag 12 has a gusseted end 21 andis a predetermined length, dependent upon the container size. Morespecifically, product dispensing bag 12 is of a length such that thepresence of product in the bag 12 brings a base 23 b (23 a is thestarting position) of the gusset 21 into contact with the bottom 22 ofthe container 13, which may be dome shaped. The gusset 21 serves toprevent undue force on a seal between the valve 10 and the bag 12 whenproduct 25 is in the bag. Furthermore, the gusset 21 improves bag fillcapacity of the product 25 for a given can size. Preferably, the heightof the gusset 21 (distance between the bottom of the bag and interiorseam of the gusset) extends for approximately 80% of the radius of thecontainer.

FIG. 2 depicts a non-limiting exemplary embodiment of a spray package502 having a metered-dose valve assembly 101. Metered-dose valveassembly 101 has a dip tube 15 which provides a flow channel fordelivery of a product (e.g., underarm product) to the valve housing 201.Valve housing 201 provides a volumetric chamber for product containmentand also has a mechanical assembly area for supporting the spring 30 andstem 35. Spring 30 and stem 35 may be constructed as individual orcombined parts. Spring 30 provides an energy constant to return the stem35 to a closed/sealed position. Stem 35 provides a connection betweenvalve housing 201 and actuator 90. In the metered valve, the stem 35provides the function of shut off of the flow of product from the diptube 15 and the valve housing 20. This shut off operation is achieved bydesigning stem 35 such that its bottom end impacts the top of dip tube15 or bottom end of the valve housing 201 at the time of or before thestem orifice 80 opens. By designing the opening and shut off functionsin this manner, only the product contained within the valve housing 201is dispensed. Ferrule 40 mechanically fastens the metered-dose valveassembly 101 to container body 70. Valve gasket 50 provides a sealbetween ferrule 40 and container body 70. Stem gasket 60 provides a sealbetween valve housing 201 and ferrule 40, as well as a seal between stemorifice 80 and the flow of the product. Each of the gaskets in theMetered-dose valve assembly 101 may be compressed to conform betweensurfaces. For valve gasket 40, compression minimizes any potentialleakage between ferrule 40 and container body 70. For stem gasket 60,compression minimizes any potential leakage between valve housing 201and the environments or to stem orifice 80. Stem orifice 80 provides aflow channel from valve housing 201 to actuator 90.

FIG. 3 depicts an example embodiment of a continuous-flow valve assembly110. Continuous-flow valve assembly 110 has a dip tube 115 whichprovides a flow channel for delivery of a product (e.g., scalpmedication) to the valve housing 120. Valve housing 120 has a mechanicalassembly area for supporting the spring 301 and stem 351. Spring 301 andstem 351 may be constructed as individual or combined parts. Spring 301provides an energy constant to return the stem 351 to a closed/sealedposition. Stem orifice 180 provides a flow channel from valve housing201 to actuator 190. Depressing of actuator 190 causes product to besprayed in a continuous fashion from the package. Exit channel 195 withits valve diameter orifice provides an exit flow channel for the flow ofproduct just before it is sprayed. It is this valve diameter orificethat is desirably about 0.001-0.10 inches, more preferably about0.001-0.015 inches and most preferably about 0.001-0.010 inches.

To appreciate the present invention, one should recognize that themetered-dose valve assembly 101 only allows for a metered dose such thatthe amount of product delivered is controlled (e.g., controlled by thevolume of the valve housing 201). In contrast, the continuous-flow valveassembly 100 and 110 does not control the amount dosed, rather theamount of product delivered is dependent upon the duration of time thatthe consumer depresses actuator 190. It should also be appreciated byone skilled in the art that the design of metered-dose valve assembly101 may be altered in a variety of ways but that the importantcharacteristic is that the valve assembly used must deliver controlledvolumes of product (i.e., not a continuous spray).

It has also been determined that certain sizing relationships for thebag, the gusset, and the valve assembly further enhance thecharacteristics of the dispensing system. The bag height should beapproximately equal to the difference between the inside can height(from the top rim of the container to the top surface of the bottomdome) and the valve height. Preferably, the material length isapproximately equal to the sum of twice the bag height, and two timesthe gusset length.

Further reference is made to the following prophetic and actual examplesof continuous spray medication compositions.

PROPHETIC EXAMPLE I

A 2% v/v solution of minoxidil can be prepared using the followingcarrier solutions:

Carrier 1:

Ingredient % v/v SD alcohol, ethanol or isopropanol 60.0 propyleneglycol, glycerin and/or dimethyl-isosorbide 20.0 purified water 20.0

Carrier 2:

Ingredient % v/v SD alcohol, ethanol or isopropanol 16.8 propyleneglycol, glycerin and/or dimethyl-isosorbide 20.0 purified water 63.2

Procedure

In separate mixing vessels, add the carrier solutions. Then add milledminoxidil until they are in a 2% v/v (for higher concentrations ofminoxidil, proportionately higher amounts of the propylene glycol,glycerin and/or dimethyl-isosorbide would be expected to be used)solution in each mixing vessel. Continue mixing until all ingredientsare added and dissolved. Add concentrate to aerosol can and charge withpropellant or propellant source.

Valving

Vendor: SeaquistPerfect Vapor Tap: None Type: XT 91 Tubing ID: 0.122″Stem Orifice: 0.013″ Actuator: EUROSTAR ST VALVE Spring: 0.025″ SS0.015″ DU3832 Body Orifice: 0.13″ XT Standard

PROPHETIC EXAMPLE 2

The following are two examples of metered-dose valve assemblies:

-   -   Manufactured by: Seaquist    -   Part #: MV20-25    -   25 MCL Metered Body    -   0.020″ Stem    -   Buna-P Diaphragm    -   0.021″ Spring    -   Buna-P Liner    -   Ferrule: Un-Anodized    -   Capillary 0.045″ I.D. Dip Tube, Cut to 4″ Length    -   Manufactured by: Seaquist    -   Part #: MV20-185    -   185 MCL Metered Body    -   0.020″ Stem    -   Buna-P Diaphragm    -   0.021″ Spring    -   Buna-P Liner    -   Ferrule: Un-Anodized    -   Capillary 0.045″ I.D. Dip Tube, Cut to 4″ Length

ACTUAL EXAMPLE 3

A bag-in-can package supplied by CCL Container, Canada (now Seaquist)was prepared with #10 cans and 30 psi pressure (compressed air) prior tofilling the bag with 1 oz. 5% minoxidil (OTC). The pressure rose to 100psi when the bag was full. Two actuator valve sizes of 0.009 inches and0.013 inches were interchangeably used on the same can to produce thefollowing data (gassing was observed visually).

ACTUAL DISPENSE VALVE SIZE TIME TO VOLUME RATE (INCHES) DISPENSE (ML)(ML/SEC) GASSING .009 1.97 1.0 .5 LOW 2.41 1.2 .49 LOW 1.97 1.0 .5 LOW.013 2.28 2.4 1.05 LOW 2.1 2.0 .95 LOW

Because of the goal of dispensing about 1 mL of product within about 1-5seconds, preferably about 1-3 seconds, and more preferably, about 2seconds, the 0.009 inch valve appears to provide the closest match foroptimal performance, low gassiness (preferably less than 5% respirabledrops per mL of dispensing) and ideal dosage within typical consumeractuation time limits. Ideally, the actuator valve should be less than0.015 inches in diameter, and more preferably less than 0.010 inches indiameter, with flow rates of about 0.2-1 mL/sec or less, and preferablyabout 0.5 mL/sec or less. The actuator valve diameter is generally lessthan 0.10 inches to prevent accidental overdosing, but greater than0.001 inches to minimize gassing. More preferably, the valve actuatordiameter can be less than 0.015 inches and greater than 0.001 inches,and especially about 0.006, 0.007, 0.008 and 0.009 inches in diameter.

Although the invention has been described in terms of exemplaryembodiments, it is not limited thereto. Rather, the appended claimsshould be construed broadly to include other variants and embodiments ofthe invention that may be made by those skilled in the art withoutdeparting from the scope and range of equivalents of the invention.

1. A spray delivery system in combination with a dosage-sensitiveprescribed medication, comprising: a portable container having a gasimpervious container wall; a pressure source disposed within saidcontainer; a selectively operable valve assembly affixed to saidcontainer; and a prescribed medication in liquid form disposed withinsaid container, said prescribed medication comprising an activeingredient in an amount sufficient to treat a patient within apharmacologically acceptable carrier solution; whereby said valveassembly produces a sprayed dosage of said prescribed medication withinabout 5 seconds following a single operation of said valve assembly,wherein said spray is generated by a pressurizing agent compressing on aproduct bag of continuous spray package containing said prescribedmedication so that the spray contains no portion of said propellant;wherein said portable container and selectively operable valve assemblyform part of metered dose system.
 2. The delivery system of claim 1,wherein said valve assembly has an actuator valve diameter of less than0.10 inches, but greater than 0.001 inches.
 3. The delivery system ofclaim 1 wherein said valve assembly has an actuator valve diameter ofless than 0.015 inches and greater than 0.001 inches.
 4. The deliverysystem of claim 1 wherein said valve assembly has an actuator valvediameter of less than 0.010 inches and produces a flow rate of less thanabout 1 mL/second.
 5. The delivery system of claim 1 wherein saiddosage-sensitive prescribed medication is for topical administrationonly.
 6. The delivery system of claim 1 wherein said spray is deliveredquietly, under 30 decibels.
 7. A spray delivery system for delivering adosage-sensitive prescribed medication for topical administration,comprising: a portable container having a gas impervious container wall;a pressure source disposed within said container; a selectively operablevalve assembly affixed to said container; and a prescribed medication inliquid form disposed within said container, said prescribed medicationcomprising an active ingredient in an amount sufficient to treat apatient within a pharmacologically acceptable carrier solution; wherebysaid valve assembly comprises an actuator valve, said valve assemblyproduces a sprayed dosage of said prescribed medication within about 5seconds following a single operation of said valve assembly, whereinsaid spray is generated by a pressurizing agent compressing on a productbag of continuous spray package containing said prescribed medication sothat the spray contains no portion of said propellant.